Reduction of bloodstream infections from oral organisms in pediatric stem cell transplant: a randomized, multicenter, double-blind, placebo-controlled study evaluating twice daily oral xylitol

减少儿科干细胞移植中口腔生物体的血流感染：一项随机、多中心、双盲、安慰剂对照研究，评估每日两次口服木糖醇

• 批准号: 10176918
• 负责人: Christopher Eugene Dandoy
• 金额: $ 49.02万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-06 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176918
• 关键词: Adherence; Admission activity; Adopted; Bacteremia; Bacteria; Bacterial Translocation; Blood Circulation; Bone Marrow Transplantation; Childhood; Clinical; Clinical Trials; Communicable Diseases; Data; Dental; Dental Plaque; Dentists; Diagnosis; Double-Blind Method; Fiber; Funding Opportunities; Gingiva; Gingivitis; Goals; Healthcare; Immune System Diseases; Incidence; Infection; Inflammation; Injury; Intensive Care Units; Intervention; Morbidity - disease rate; Mucositis; Mucous Membrane; Multi-Institutional Clinical Trial; National Institute of Dental and Craniofacial Research; Oral; Oral Ulcer; Oral cavity; Oral mucous membrane structure; Organism; Pathogenicity; Patients; Physicians; Population; Positioning Attribute; Prevention; Prevention strategy; Randomized; Research; Route; Saliva; Secondary to; Sepsis; Septic Shock; Specialist; Stem cell transplant; Streptococcus mitis; Sugar Alcohols; Testing; Time; Transplant Recipients; U-Series Cooperative Agreements; United States; Work; Xylitol; arm; base; clinically relevant; control trial; cost estimate; effectiveness evaluation; expectation; fruits and vegetables; graft vs host disease; improved outcome; injured; innovation; microbial; microbiome analysis; mortality; oral bacteria; oral care; oral infection; oral microbiome; oral plaque; placebo controlled study; preservation; prevent; response; standard of care; Adherence; Admission activity; Adopted; Bacteremia; Bacteria; Bacterial Translocation; Blood Circulation; Bone Marrow Transplantation; Childhood; Clinical; Clinical Trials; Communicable Diseases; Data; Dental; Dental Plaque; Dentists; Diagnosis; Double-Blind Method; Fiber; Funding Opportunities; Gingiva; Gingivitis; Goals; Healthcare; Immune System Diseases; Incidence; Infection; Inflammation; Injury; Intensive Care Units; Intervention; Morbidity - disease rate; Mucositis; Mucous Membrane; Multi-Institutional Clinical Trial; National Institute of Dental and Craniofacial Research; Oral; Oral Ulcer; Oral cavity; Oral mucous membrane structure; Organism; Pathogenicity; Patients; Physicians; Population; Positioning Attribute; Prevention; Prevention strategy; Randomized; Research; Route; Saliva; Secondary to; Sepsis; Septic Shock; Specialist; Stem cell transplant; Streptococcus mitis; Sugar Alcohols; Testing; Time; Transplant Recipients; U-Series Cooperative Agreements; United States; Work; Xylitol; arm; base; clinically relevant; control trial; cost estimate; effectiveness evaluation; expectation; fruits and vegetables; graft vs host disease; improved outcome; injured; innovation; microbial; microbiome analysis; mortality; oral bacteria; oral care; oral infection; oral microbiome; oral plaque; placebo controlled study; preservation; prevent; response; standard of care

Abstract Bloodstream infections (BSI) caused by bacteria translocating across injured mucosa are a significant cause of morbidity and mortality in the 25,000 patients undergoing stem cell transplantation (SCT) in the United States each year. BSI secondary to translocation of oral organisms through damaged oral mucosaoccurs in nearly 16% of SCT recipients in the first three weeks after SCT despite current routine oral care. There are currently no known strategies to prevent post-SCT BSI from the translocation of bacteria through an injured mucosa. There is a critical need to identify preventive strategies to reduce BSI, and the oral mucosa as a specific route of entry has not been evaluated. In the absence of such information, SCT patients will continue to develop BSI from translocation of bacteria from mucosal barrier injury. Our long-term goal is to develop and disseminate clinically relevant and easily adoptable strategies to prevent BSI and improve outcomes after SCT. The overall objective of this proposal is to identify a clinically effective strategy to prevent or reduce BSI secondary to bacterial translocation through injured mucosa in the mouth. The rationale for the study is based on our baseline and pilot intervention data. The central hypothesis is that dental xylitol use, in addition to current oral care practice, are effective at reducing BSI from oral organisms, and decreasing the incidence of gingivitis, oral plaque, and oral ulcerations after SCT. Apart from our preliminary data, we are well-positioned to carry out the proposed work as we have a multicenter collaborative team consisting of pediatric bone marrow transplant physicians, dentists, and infectious disease specialists with focus and expertise in microbiome analyses. The following specific aims are proposed: AIM 1: Determine the effectiveness of twice-daily xylitol-wipe application on reducing BSI from oral organisms through a randomized, multicenter, double-blind, placebo-controlled study in pediatric SCT recipients. AIM 2: Determine the effectiveness of twice-daily xylitol-wipe application in reducing dental plaque, mucositis, oral GVHD, and gingival inflammation. AIM 3: Evaluate the influence of twice-daily xylitol-wipe application on oral microbiome diversity and saliva levels of pathogenic microbial species. The innovation of this proposal lies in the simplicity and affordability of the intervention. Xylitol is commercially available, inexpensive ($0.15 per application), non-toxic, and can be rapidly adopted into practice. If our hypotheses are proven, xylitol application could reduce the morbidity and mortality associated with BSI and decrease healthcare-associated costs of an estimated $40,000 per infection. At the successful completion of the proposed research, our expectation is to have demonstrated a significant reduction of bacteremia from oral organisms (Aim 1); decreased oral dental plaque, gingivitis, and oral ulceration (Aim 2); and preserved oral microbiome diversity and reduction of pathogenic microbial species in the oral cavity in those receiving daily dental xylitol wipe application (Aim 3) leading to substantial changes to the prevention of BSI in this population.

抽象的 由跨受伤粘膜易位的细菌引起的血液感染（BSI）是 美国接受干细胞移植（SCT）的25,000例患者的发病率和死亡率 每年。通过近16％的口服粘膜损坏的口服粘液易生易位的BSI。 尽管当前的常规口服护理，但在SCT之后的前三周，SCT接受者的sct受体。目前没有 可防止SCT BSI通过受伤的粘膜易位的已知策略。那里 是确定减少BSI的预防策略的迫切需要，而口腔粘膜作为特定的进入途径 尚未评估。在没有此类信息的情况下，SCT患者将继续从 粘膜屏障损伤中细菌的易位。我们的长期目标是在临床上开发和传播 相关且易于采用的策略，以防止BSI并改善SCT后的结果。总体目标 该建议的内容是确定一种临床有效的策略，以防止或减少细菌继发的BSI 通过嘴里受伤的粘膜易位。该研究的理由是基于我们的基线和飞行员 干预数据。中心假设是，除了目前的口腔护理实践外，木糖醇的使用是 有效减少口服生物的BSI，并降低牙龈炎，口腔斑块和口服的发生率 SCT后的溃疡。除了我们的初步数据外，我们还可以很好地进行拟议的工作 由于我们有一个多中心协作团队，包括小儿骨髓移植医师，牙医， 以及在微生物组分析中具有重点和专业知识的传染病专家。以下特定目标 提出了：目标1：确定每天两次木糖醇含量应用在降低BSI中的有效性 通过随机，多中心，双盲，安慰剂对照研究的口服生物在小儿SCT中 收件人。 AIM 2：确定每天两次木糖醇含量在减少牙齿斑块中的有效性， 粘膜炎，口服GVHD和牙龈炎症。 AIM 3：评估每天两次木糖醇饮用的影响 在口腔微生物组多样性和致病微生物物种的唾液水平上应用。这个创新 建议在于干预的简单性和负担能力。木糖醇是市售的，便宜的 （每个应用程序0.15美元），无毒，可以迅速采用。如果证明了我们的假设，木糖醇 应用可以降低与BSI相关的发病率和死亡率，并减少与医疗保健相关的 每次感染估计40,000美元的成本。在成功完成拟议的研究时，我们 期望表明口服生物的菌血症显着降低（AIM 1）； 口服牙菌斑，牙龈炎和口腔溃疡减少（AIM 2）；并保留口服微生物组的多样性 并减少接受每日木制木醇擦拭人员口腔中的致病微生物物种 应用（目标3）导致预防该人群中BSI的实质性变化。